Antagonism to muscarinic receptors are known to cause bronchodilation, gastrointestinal hypanakinesis, gastric hyposecretion, dry mouth, mydriasis, suppression of bladder contraction, hypohydrosis, tachycardia and the like [cf. “Basic and Clinical Pharmacology, 4th ed., (APPLETON & LANGE), pp.83-92, (1989); and Drug News & Perspective, 5(6), pp.345-352 (1992)].
It has been made clear through recent studies that there are at least three subtypes of muscarine receptors (M1 receptors, M2 receptors and M3 receptors); which receptors are present in tissues or organs at different distribution patterns. M1 receptors are present mainly on the brain; M2 receptors, on the heart; and M3 receptors, on the smooth muscles and glandular tissues. Whereas, all of the large number of compounds heretofore known to exhibit antagonism to muscarinic receptors antagonize these three subtypes of muscarinic receptors non-selectively. Consequently, in oral administration of these compounds as therapeutic or prophylactic agents for treatment of diseases of, for example, the respiratory system, in addition to such side effects as dry mouth, nausea and mydriasis, serious side effects associated with the central nervous system, such as dementia, induced particularly by M1 receptors and those associated with the heart, such as tachycardia caused by M2 receptors present problems.
Currently, administration by inhalation of non-selective muscarine antagonists as therapeutic or prophylactic agents for respiratory diseases is clinically applied. However, those medicines are subject to the problems that durability of their action is short and their inhalation plural times per day is necessary, and also that they have such side effects as tachycardia and dry mouth attributable to the non-selectivity of said receptors.
As compounds having a structure resembling that of the compounds of the present invention, for example, those described in JP-Hei 1 (1989)-131145A or in Farmaco, Vol.47, No.9, pp.1133-1147 (1992) can be cited, which, however, neither concretely disclose nor suggest the compounds of the present invention.